کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10594733 | 981848 | 2010 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Acylurea connected straight chain hydroxamates as novel histone deacetylase inhibitors: Synthesis, SAR, and in vivo antitumor activity
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Thirty-six novel acylurea connected straight chain hydroxamates were designed and synthesized. Structure-activity relationships (SAR) were established for the length of linear chain linker and substitutions on the benzoylurea group. Compounds 5g, 5i, 5n, and 19 showed 10-20-fold enhanced HDAC1 potency compared to SAHA. In general, the cellular potency pIC50 (COLO205) correlates with enzymatic potency pIC50 (HDAC1). Compound 5b (SB207), a structurally simple and close analogue to SAHA, is more potent against HDAC1 and HDAC6 compared to the latter. As a representative example of this series, good in vitro enzymatic and cellular potency plus an excellent pharmacokinetic profile has translated into better efficacy than SAHA in both prostate cancer (PC3) and colon cancer (HCT116) xenograft models.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 11, 1 June 2010, Pages 3314-3321
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 11, 1 June 2010, Pages 3314-3321
نویسندگان
Haishan Wang, Ze-Yi Lim, Yan Zhou, Melvin Ng, Ting Lu, Ken Lee, Kanda Sangthongpitag, Kee Chuan Goh, Xukun Wang, Xiaofeng Wu, Hwee Hoon Khng, Siok Kun Goh, Wai Chung Ong, Zahid Bonday, Eric T. Sun,